Heart rate recovery (HRR) is an important indicator of cardiovascular health. The purpose of the present investigation is to examine the influence of sex on the relationship between HRR and other markers of cardiovascular health. Two hundred and seventy-five apparently healthy subjects participated in this study. Subjects underwent cardiopulmonary exercise testing (outcome measures: VO(2max) and HRR 1 and 2 min into recovery), lipid analysis, measurement of resting systolic and diastolic blood pressure and measurement of aortic wave velocity (AWV in m/s) via magnetic resonance. HRR both at 1 min (HRR(1)) and at 2 min (HRR(2)) were higher in males. In general, the correlation between HRR(1) and other measures of interest was weaker than that found with HRR(2) in both male and female subjects. With respect to HRR(2), the relationship with other measures of interest was stronger in the female subgroup. Specific to arterial stiffness, the correlation between HRR(2) and AWV was -0.33 and -0.46 (P<0.001 for both) in male and female subgroups, respectively. The results of the present study indicate that both gender and the timing of HRR measurement influence its relationship with other important cardiovascular risk factors.

Introduction: The chemokine receptor CCR7 plays a pivotal role in the recruitment of native T cells and antigen-activated dendritic cells (DCs) to secondary lymphoid organs. As antigen presentation and T cell recruitment are crucial events in allograft rejection, the aim of this study was to investigate the impact of CCR7 on the development of transplant arteriosclerosis.

Introduction: The chemokine receptor CCR7 plays a pivotal role in the recruitment of T cells and dendritic cells to secondary lymphoid organs. In contrast, CXCR5 controls B cell migration and the organization of B cell follicles. The aim of this study was to investigate the impact of CCR7 and CXCR5 on the development of transplant arteriosclerosis (TxA).

Introduction: The chemokine receptor CCR7 has been shown to play a pivotal role in the recruitment of native T cells and antigen-activated dendritic cells (DCs) to secondary lymphoid organs. As antigen presentation and T cell recruitment are both crucial events in allograft rejection, the aim of this study was to investigate the impact of CCR7 on the development of transplant arteriosclerosis, the hallmark feature of chronic rejection.

[7-(Dimethylamino)coumarin-4-yl]methyl (DMACM) and [7-(diethylamino)coumarin-4-yl]methyl (DEACM) esters of 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and 8-bromoguanoyclic monophosphate (8-Br-cGMP) are described as novel sine 3',5,-cyclic monophosphate (8-Br-cGMP) are described as novel caged compounds for 8-bromo-substituted cyclic nucleotides. Synthesis is accomplished by treatment of the free acids of the cyclic nucleotides with the corresponding 7-(dialkylamino)-substituted 4-(didzomethyl)coumarins. Irradiation of the DMACM- and DEACM-caged cyclic nucleotides with UV light stimulates the release of the cyclic nucleotides within toughly a nanosecond The new caged compounds are resistant to hydrolysis in aqueous buffers and exhibit long-wavelength absorption properties with maxima at 400 nm, high extinction coefficients, and high quantum yields (0.15-0.31). Their favorable properties render these compounds the most efficient and rapid phototriggers of 8-bromosubstituted cyclic nucleotides known. The usefulness of the compounds for physiological studies under nondamaging light conditions was examined in HEK293 cells expressing the alpha subunit of the cyclic-nucleotide-gated (CNG) channel of cone photoreceptors (CNGA3) and of olfactory neurons (CNGA2) by using confocal laser scanning microscopy and the patch clamp technique.

Photoaktivierbare cyclische Nucleotide mit außerordentlich vorteilhaften Eigenschaften wurden unter Verwendung neuer photolabiler Cumarinylmethyl-Schutzgruppen entwickelt (siehe Schema). Sie dienen als ausgezeichnete intrazelluläre Quellen für cAMP und cGMP und ermöglichen die Untersuchung raum- und zeitabhängiger Aspekte der von cyclischen Nucleotiden abhängigen Signaltransduktion.

Caged cyclic nucleotides exhibiting remarkable advantageous properties have been developed through the use of novel photolabile coumarinylmethyl protecting groups (see scheme). They serve as excellent intracellular sources of cAMP and cGMP and allow the study of spatial- and time-dependent aspects of cyclic nucleotide signaling.

New caged derivatives of hydrolysis-resistant 8-bromoadenosine cyclic 3',5'-monophosphate (8-Br-cAMP) and 8-bromoguanosine cyclic 3',5'-monophosphate (8-Br-cGMP) are described. The compounds are the axial and equatorial isomers of the (7-methoxycoumarin-4-yl)methyl (MCM) esters of cyclic nucleotides. Synthesis is accomplished by treatment of 4-bromomethyl-7-methoxycoumarin with the tetra-n-butylammonium salts of the 8-bromo-substituted cyclic nucleotides or with the free acids of 8-Br-cAMP and 8-Br-cGMP in the presence of silver(I) oxide. MCM-caged 8-Br-cAMP and MCM-caged 8-Br-cGMP liberate 8-Br-cAMP and 8-Br-cGMP during irradiation with ultraviolet light within a few nanoseconds. They show favorable absorption properties and quantum yields and are resistant to hydrolysis in aqueous buffer solutions. The moderate fluorescence properties of the caged compounds in comparison with the strongly fluorescent 4-hydroxymethyl-7-methoxycoumarin (MCM-OH) photoproduct allow the indirect estimation of the amount of photolytically released cyclic nucleotides in aqueous buffer solutions using fluorescence measurements. Their usefulness for physiological studies has been examined in a mammalian cell line expressing the cyclic nucleotide-gated ion channel of bovine olfactory sensory neurons using the patch-clamp technique and confocal laser scanning microscopy. The caged compounds serve as efficient and rapid intracellular sources of 8-Br-cAMP and 8-Br-cGMP. However, at least in HEK 293 cells, fluorescence signals cannot be used to monitor the photolysis of MCM-caged 8-Br-cAMP and 8-Br-cGMP, due to quenching of the fluorescence of MCM-OH.

Dimethylamino-cyano-diphenylbutadiene (DCB) has been investigated using photochemical and photophysical techniques. HPLC analysis enabled the separation of two photoisomers. Their absorption spectra and extinction coefficients were determined by combining the diode array spectra with the isosbestic points observed in photolysis. The forward and backward quantum yields of photoisomerization were determined. The quantum-chemical modelling of these spectra allowed for a tentative assignment of the photoisomers to the mono-cis isomers ct and tc. Fluorescence lifetimes and quantum yields allowed the conclusion of a negative solvatokinetic behaviour of the nonradiative decay. Catalyzed thermal isomerization of DCB was observed on reversed-phase chromatographic material.

We present the spectroscopic, fluorescence and photochemical properties of novel caged cyclic nucleotides, the axial and equatorial (7-methoxycoumarin-4-yl)methyl esters of cGMP, 8-Br-cGMP, cAMP and 8-Br-cAMP. The deactivation of the locally excited state of the caged compound is characterized by the competition between fluorescence and photochemical ester cleavage resulting in a strong fluorescence quenching. The fluorescence quenching rate is determined by the specific nucleic base and by the conformation. During photochemical ester cleavage and formation of 4-hydroxymethyl-7-methoxycoumarin the fluorescence intensity of the solution increases up to 50 fold and more. This photochemical fluorescence enhancement is used for the visualization of local distribution of liberated biologically active cyclic nucleotide using confocal laser scanning microscopy.

The photolysis of DNQ-4-sulfonic acid esters yields 3-indenecarboxylic acid-1-sulfonic ester (3-ICA-1-SE), 3-ICA-1-SE reads to the corresponding sulfonic acid. The rate of the ester cleavage is fast at exposure and slow in the dark. The deep UV lamp or laser exposure using low intensify is most effective for acid generation, pH change and network formation (image reversal).

We investigated the spectroscopic, photophysical, and photochemical properties of novel caged cyclic nucleotides, the axial and equatorial (7-methoxycoumarin-4-yl)methyl esters of cGMP and of 8-Br-cGMP. The competition between fluorescence and photochemical ester cleavage results in a strong quenching of the coumarin fluorescence. This fluorescence quenching is enhanced additionally by the donor–acceptor interaction between the coumarin unit and the nucleic base, pronounced in the axial configuration. On photochemical decaging the fluorescence intensity increases up to 48-fold and more. This photochemical fluorescence enhancement can be used for the description of the temporal and local distribution of biologically active cGMP derivatives.

Bi-and trichromophoric 1,2-Diazonaphthoquinone systems (DNQ systems) are characterized by a non-reciprocity behaviour which means that the rate of photolytic cleavage depends on the concentrations of starting compounds and intermediates of the photodecomposition, and the quantum yield changes with progressing reaction. The photolysis (lambda = 436 nm) of the asymmetrically substituted model compound, which contains two chromophores of various reactivity (DNQ4 and DNQ5) at one benzophenone back-bone molecule, effects a sequential photolytic mechanism. The excitation energy is transferred from the local excited DNQ5 (donor) to the DNQ4 (acceptor). Different molecular environments were found for each DNQ-chromophore in di- and tri-(DNQ-5-sulfonyl-oxy)-benzophenone, detected by H-1-, C-13-, N-15-NMR, quantum chemical calculations and single-crystal X-ray analysis. The effect of the change in the electronic structure on the photoreactivity is distinct in particular of 2-DNQ chromophore. An energy transfer between all DNQ chromophores exists.

We have previously shown that 24,25‐(OH)2D3 plays a major role in resting zone (RC) chondrocyte differentiation and that this vitamin D metabolite regulates protein kinase C (PKC). The aim of the present study was to identify the signal transduction pathway used by 24,25‐(OH)2D3 to stimulate PKC activation. Confluent, fourth passage RC cells from rat costochondral cartilage were used to evaluate the mechanism of PKC activation. Treatment of RC cultures with 24,25‐(OH)2D3 for 90 min produced a dose‐dependent increase in diacylglycerol (DAG). Addition of R59022, a diacylglycerol kinase inhibitor, significantly increased PKC activity in cultures treated with 24,25‐(OH)2D3. Addition of dioctanoylglycerol (DOG) to plasma membranes isolated from RC increased PKC activity 447‐fold. Addition of pertussis toxin or cholera toxin to control cultures elevated basal PKC activity. When added together with 10−9 M 24,25‐(OH)2D3, there was an additive effect on PKC activity but in cultures treated with 10−8 M 24,25‐(OH)2D3, only the hormone‐dependent stimulation of PKC was observed. The phospholipase C inhibitor, U73‐122, had no effect on PKC activity, indicating that the DAG produced in response to 24,25‐(OH)2D3 is not derived from phosphatidylinositol. Addition of the tyrosine kinase inhibitor, genistein, also had no effect on 24,25‐(OH)2D3‐stimulated PKC, further supporting the hypothesis that phospholipase C is not involved in the mechanism and that phospholipase D is responsible for the increase in DAG production. Phospholipase A2 inhibitors, quinacrine and AACOCF3, and the cyclooxygenase inhibitor indomethacin increased PKC activity in the RC cultures. Exogenous PGE2, one of the downstream products of phospholipase A2 action, inhibited PKC activity. These results suggest that 24,25‐(OH)2D3 regulates PKC activity by two distinct phospholipid‐dependent mechanisms: production of DAG via phospholipase D and inhibition of the production of PGE2 via inhibition of phospholipase A2 and cyclooxygenase. © 1996 Wiley‐Liss, Inc.

A series of AZ-compatible negative photoresists composed of a novolak resin and azide sensitizers for the micro and nano-lithography is presented. The ma-N 2400 and ma-N 300 are sensitive to light of the deep UV region (248 nm, 254 nm, 308 nm), the ma-N 400 and ma-N 1400 are sensitive to light of the mid UV region, the latter has a high sensitivity to the i-line (365 nm). The thickness of the resist layers prepared by spin coating is up to 8 micrometers depending on the composition of the resist solution. All resists are non-swelling during aqueous alkaline development after exposure. Using special lithography, these photoresists have a resolution capability up to 0.1 micrometers . The resistance to wet etch solutions and to dry etch gases is superior and higher than that of the most positive resists based on novolak.

At laser excitation of E-4,4'-di(fluorescein-6-yl-thioureanyl)-stilbene (Ar+ Laser, lambda(exc) = 488 nm) a simultaneous two photon energy transfer (SET) goes on from the excited fluorescein chromophores to the stilbene. Beside the fluorescence of the fluorescein the fluorescence of the locally excited stilbene, caused by SET, and the E-Z isomerization are observed.